Anthrax vaccines and delivery methods

Abstract

Immunogenic anthrax compositions, such as anthrax vaccines, and methods for delivering immunogenic anthrax compositions and/or vaccines to a mammal. Methods include delivery to mucosal membranes and to skin.

1 - 89 . (canceled)  
   
   
       90 . An immunogenic anthrax composition made by a method comprising 
 (i) atomizing a liquid formulation of an immunogenic anthrax composition to produce an atomized formulation,    (ii) freezing said atomized formulation to form solid particles, and    (iii) drying said solid particles to obtain dried particles.    
   
   
       91 . The method of  claim 90  wherein said dried particles have a volume mean diameter of between about 35 μm and about 300 μm, wherein at least about 50% of said dried particles have a volume diameter within about 80% of the mean, and said dried particles have a mean aerodynamic diameter of between about 8 μm and about 140 μm.  
   
   
       92 . The immunogenic anthrax composition of  claim 90  that is an anthrax vaccine.  
   
   
       93 . The anthrax vaccine of  claim 92  that is an Anthrax Vaccine Absorbed (AVA) vaccine.  
   
   
       94 . The anthrax vaccine of  claim 92  that is a recombinant protective antigen (rPA) vaccine.  
   
   
       95 . The anthrax vaccine of  claim 92  that comprises an adjuvant.  
   
   
       96 . The anthrax vaccine of  claim 92  that does not contain an adjuvant.  
   
   
       97 . The anthrax vaccine of  claim 92 , wherein said dried particles have a volume mean diameter of between about 50 μm and about 300 μm.  
   
   
       98 . The anthrax vaccine of  claim 92 , wherein said liquid formulation of said anthrax vaccine consists essentially of said anthrax vaccine and water.  
   
   
       99 . An anthrax vaccine prepared by atomizing a liquid formulation of an anthrax vaccine to produce an atomized formulation, such that, following freezing of said atomized formulation to form solid particles, and drying of said solid particles to produce dried particles, said dried particles have an average mean diameter of between about 35 μm and about 300 μm, at least about 50% of said dried particles have a volume diameter within about 80% of the mean, and said dried particles have a mean aerodynamic diameter of between about 8 μm and about 140 μm.  
   
   
       100 . An anthrax vaccine that comprises an immunogenic agent and at least one pharmaceutically acceptable carrier in the form of dried particles having a mean aerodynamic diameter of between about 8 μm and about 140 μm and a volume mean diameter of between about 35μ and about 300μ, wherein at least about 50% of said dried particles have a volume diameter within about 80% of the mean,.  
   
   
       101 . The anthrax vaccine of  claim 100  that is an AVA vaccine.  
   
   
       102 . The anthrax vaccine of  claim 100 , which is an rPA vaccine.  
   
   
       103 . The anthrax vaccine of  claim 92 , made by a method comprising 
 (i) atomizing a liquid formulation of an anthrax vaccine composition to produce an atomized formulation which comprises droplets having an average mean diameter of between about 35μ and about 300μ,    (ii) freezing said atomized formulation to form solid particles, and    (iii) drying said solid particles to obtain dried particles.    
   
   
       104 . The vaccine of  claim 103 , wherein said dried particles have a volume mean diameter of between about 35 μm and about 300 μm, at least about 50% of said dried particles have a volume diameter within about 80% of the mean, and said dried particles have a mean aerodynamic diameter of between about 8 μm and about 140 μm.  
   
   
       105 . A method of preparing an anthrax vaccine, comprising 
 (i) atomizing a liquid formulation of an anthrax vaccine composition to produce an atomized formulation,    (ii) freezing said atomized formulation to form solid particles, and    (ii) drying said solid particles to obtain dried particles.    
   
   
       106 . The method of  claim 105 , wherein said dried particles have an average mean diameter of between about 35 μm and about 300 μm, at least about 50% of said dried particles have a volume diameter within about 80% of the mean, and said dried particles have a mean aerodynamic diameter of between about 8 μm and about 140 μm.  
   
   
       107 . The method of  claim 106 , wherein said dried particles have a volume mean diameter of between about 50 μm and about 300 μm.  
   
   
       108 . The method of  claim 105 , wherein said liquid formulation of said anthrax vaccine composition consists essentially of said anthrax vaccine and water.  
   
   
       109 . A method of preparing an anthrax vaccine, comprising atomizing a liquid formulation of an anthrax vaccine composition to produce an atomized formulation, such that, following freezing of said atomized formulation to form solid particles, and drying of said solid particles to produce a powder, the dried powder comprises dried particles having an average mean diameter of between about 35μ and about 300μ, at least about 50% of said dried particles have a volume diameter within about 80% of the mean, and said dried particles have a mean aerodynamic diameter of between about 8 μm and about 140 μm.  
   
   
       110 . A method for delivering an immunogenic anthrax composition to a mammal, comprising administering to the mammal an effective amount of the immunogenic anthrax composition of  claim 90 .  
   
   
       111 . The method of  claim 110 , wherein the immunogenic composition is an anthrax vaccine.  
   
   
       112 . The method of  claim 111 , wherein the anthrax vaccine is an Anthrax Vaccine Absorbed (AVA) vaccine.  
   
   
       113 . The method of  claim 111 , wherein the anthrax vaccine is a recombinant protective antigen (rPA) vaccine.  
   
   
       114 . The method of  claim 111 , wherein the anthrax vaccine comprises an adjuvant.  
   
   
       115 . The method of  claim 111 , wherein the anthrax vaccine does not contain an adjuvant.  
   
   
       116 . The method of  claim 111 , wherein the anthrax vaccine is administered intranasally.  
   
   
       117 . The method of  claim 110 , wherein the anthrax vaccine is administered to a mucosal membrane.  
   
   
       118 . A method for reducing the amount of an anthrax vaccine that is required to produce an efficacious result comprising administering to a patient, intranasally, an effective amount an anthrax vaccine of  claim 91 .  
   
   
       119 . A method for eliciting an immune response in a patient, comprising administering to said patient an effective amount of an immunogenic anthrax composition of  claim 90 .  
   
   
       120 . The method of  claim 119 , wherein said composition is administered intranasally.  
   
   
       121 . A method of vaccinating a patient against anthrax, comprising administering to said patient an effective amount of an immunogenic anthrax composition of  claim 90 .  
   
   
       122 . The method of  claim 121 , wherein said composition is administered intranasally.  
   
   
       123 . The method of  claim 111 , wherein the anthrax vaccine is administered as part of a prime-boost regimen.  
   
   
       124 . A method for delivering an immunogenic anthrax composition to a mammal, comprising administering the composition intradermally such that delivery of the vaccine occurs at a depth between 0.025 mm and 2.5 m in the skin of the mammal.  
   
   
       125 . The method of  claim 124  wherein the composition is administered through at least one hollow needle having an outlet with an exposed height between 0 and 1 mm, said outlet being inserted into the skin to a depth of between 0.5 mm and 2 mm.  
   
   
       126 . The method of  claim 124 , wherein the immunogenic anthrax composition is an anthrax vaccine.  
   
   
       127 . The method of  claim 126 , wherein the anthrax vaccine is an Anthrax Vaccine Absorbed (AVA) vaccine.  
   
   
       128 . The method of  claim 126 , wherein the anthrax vaccine is a recombinant protective antigen (rPA) vaccine.  
   
   
       129 . The method of  claim 126 , wherein the anthrax vaccine comprises an adjuvant.  
   
   
       130 . The method of  claim 126 , wherein the anthrax vaccine does not contain an adjuvant.  
   
   
       131 . The method of  claim 126  wherein the delivered vaccine induces an immune response in the mammal that is equal to or greater than the response after delivery of the same amount of vaccine by subcutaneous or intramuscular injection.  
   
   
       132 . The method of  claim 126  wherein the needle is a microneedle between about 31 to 50 gauge.  
   
   
       133 . The method of  claim 100  wherein the microneedle is in an array of microneedles.  
   
   
       134 . A method for improving the immunogenicity of an anthrax composition in a mammal, comprising administering the composition intradermally such that delivery of the composition occurs at a depth between 0.025 mm and 2.5 mm in the skin of the mammal.  
   
   
       135 . The method of  claim 134  wherein the anthrax composition is administered trough at least one hollow needle having an outlet with an exposed height between 0 and 1 mm, said outlet being inserted into the skin to a depth of between 0.5 mm and 2 mm.  
   
   
       136 . A method of eliciting an immune response in a patient, comprising administering intradermally to said patient an effective amount of an immunogenic anthrax composition.  
   
   
       137 . The method of  claim 136  wherein the composition is administered through at least one hollow needle having an outlet with an exposed height between 0 and 1 mm, said outlet being inserted into the skin to a depth of between 0.5 mm and 2 mm.  
   
   
       138 . A method of vaccinating a patient against anthrax, comprising administering intradermally to said patient an effective amount of an anthrax vaccine through at least one hollow needle having an outlet with an exposed height between 0 and 1 mm, said outlet being inserted into the skin to a depth of between 0.5 mm and 2 mm.  
   
   
       139 . A method for delivering an immunogenic anthrax composition into skin, comprising abrading the skin and delivering the anthrax composition into the abraded skin.  
   
   
       140 . The method of  claim 139 , wherein the skin is abraded prior to delivery of the anthrax composition.  
   
   
       141 . The method of  claim 139 , wherein the skin is abraded simultaneously with the delivery of the anthrax composition.  
   
   
       142 . The method of  claim 139 , wherein the anthrax composition is an anthrax vaccine.  
   
   
       143 . The method of  claim 142 , wherein the anthrax vaccine is an Anthrax Vaccine Absorbed (AVA) vaccine.  
   
   
       144 . The method of  claim 142 , wherein the anthrax vaccine is a recombinant protective antigen (rPA) vaccine.  
   
   
       145 . The method of  claim 142 , wherein the anthrax vaccine comprises an adjuvant.  
   
   
       146 . The method of  claim 142 , wherein the anthrax vaccine does not contain an adjuvant.  
   
   
       147 . The method of  claim 139  wherein the skin is abraded at least twice.  
   
   
       148 . The method of  claim 147  wherein the skin is abraded in alternating directions.  
   
   
       149 . The method of  claim 139  wherein the composition is applied to the skin in liquid form.  
   
   
       150 . The method of  claim 141  wherein the composition is applied to the skin from an abrading device.  
   
   
       151 . The method of  claim 150  wherein the composition is a powder, gel or film on an abrading surface of an abrading device.  
   
   
       152 . The method of  claim 151  wherein a reconstituting liquid is separately applied to the skin prior to abrasion.  
   
   
       153 . The method of  claim 151  wherein a reconstituting liquid is applied to the skin simultaneously with abrasion.  
   
   
       154 . A method for improving the immunogenicity of an immunogenic anthrax composition, comprising abrading the skin and delivering the anthrax composition into the abraded skin.  
   
   
       155 . The method of  claim 154 , which is a method for improving the protective efficacy of an anthrax vaccine.  
   
   
       156 . A method of eliciting an immune response to anthrax in a patient, comprising abrading the skin and delivering an immunogenic anthrax composition into the abraded skin.  
   
   
       157 . A method of vaccinating a patient against anthrax, comprising abrading the skin and delivering an anthrax vaccine into the abraded skin.  
   
   
       158 . A kit comprising an effective amount of a an anthrax vaccine composition of  claim 92 .  
   
   
       159 . The kit of  claim 158  that further comprises mean to administer the vaccine intranasally.  
   
   
       160 . The kit of  claim 90 , wherein the anthrax vaccine is separately packaged within the kit.  
   
   
       161 . The kit of  claim 158  further comprising: 
 a) a microabrader comprising an abrading surface, and    b) an effective amount of the anthrax vaccine.    
   
   
       162 . The kit of  claim 161 , wherein the antrax vaccine is coated on the surface of the microabrader.  
   
   
       163 . The kit of  claim 161 , wherein the anthrax vaccine is contained in a reservoir integrated with the microabrader.  
   
   
       164 . The kit of  claim 158  further comprising 
 a) a delivery device for intradermally delivering a substance to a depth between 0.025 and 2.5 mm, and    b) an effective dosage of the anthrax vaccine.    
   
   
       165 . The kit of  claim 164  wherein said delivery device comprises at least one hollow microneedle designed to intradermally deliver a substance substance to a depth between 0.025 and 2.5 mm, and the delivery device comprises, or is adapted to receive a reservoir that contains an anthrax vaccine such that the microneedle is in communication therewith.  
   
   
       166 . The kit of  claim 164  wherein the dosage is contained in a reservoir that is an integral part of, or is capable of being functionally attached to, the delivery device.  
   
   
       167 . The kit of  claim 164  wherein the hollow microneedle is between about 31 to 50 gauge.  
   
   
       168 . The kit of  claim 164  wherein the device comprises an array of microneedles.